期刊
CARTILAGE
卷 13, 期 2_SUPPL, 页码 530S-543S出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/19476035211040858
关键词
mesenchymal stem cells; chondrocytes; articular cartilage; rodent; osteoarthritis
类别
资金
- National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health [R01 AR064803]
- Freedom of Movement Award (Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison)
- NIH NIA [T32AG00021326, CTS UL1TR000427, CTS TL1TR000429]
Our study demonstrates that epigenetic reprogramming enhances the phenotypic characteristics and functions of MSCs harvested from OA patients. Additionally, reprogrammed MSCs show an improved potential for articular cartilage repair. The reprogramming strategy provides a potential solution to the challenge of variation in MSC quality.
Objectives Functions of mesenchymal stem/stromal cells (MSCs) are affected by patient-dependent factors such as age and health condition. To tackle this problem, we used the cellular reprogramming technique to epigenetically alter human MSCs derived from the synovial fluid of joints with osteoarthritis (OA) to explore the potential of reprogrammed MSCs for repairing articular cartilage. Materials and Methods MSCs isolated from the synovial fluid of three patients' OA knees (Pa-MSCs) were reprogrammed through overexpression of pluripotency factors and then induced for differentiation to establish reprogrammed MSC (Re-MSC) lines. We compared the in vitro growth characteristics, chondrogenesis for articular cartilage chondrocytes, and immunomodulatory capacity. We also evaluated the capability of Re-MSCs to repair articular cartilage damage in an animal model with spontaneous OA. Results Our results showed that Re-MSCs increased the in vitro proliferative capacity and improved chondrogenic differentiation toward articular cartilage-like chondrocyte phenotypes with increased THBS4 and SIX1 and decreased ALPL and COL10A1, compared to Pa-MSCs. In addition, Re-MSC-derived chondrocytes expressing elevated COL2A and COL2B were more mature than parental cell-derived ones. The enhancement in chondrogenesis of Re-MSC involves the upregulation of sonic hedgehog signaling. Moreover, Re-MSCs improved the repair of articular cartilage in an animal model of spontaneous OA. Conclusions Epigenetic reprogramming promotes MSCs harvested from OA patients to increase phenotypic characteristics and gain robust functions. In addition, Re-MSCs acquire an enhanced potential for articular cartilage repair. Our study here demonstrates that the reprogramming strategy provides a potential solution to the challenge of variation in MSC quality.
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